Diabetes mellitus is a serious and chronic metabolic disease that is characterized by high blood glucose (hyperglycemia) and affects millions of people world-wide. SGLT2 is a Sodium-dependent GLucose co-Transporter protein which affects the reabsorption of glucose in the kidney. It is estimated that 90% of renal glucose reabsorption is facilitated by SGLT2. Since glucose reabsorption is mediated predominantly by SGLT2 and because high glucose levels have been identified as a cause of disease in diabetes, SGLT2 has become a drug target for type 2 diabetes therapy. Selective inhibition of SGLT2 has the potential to reduce hyperglycemia by inhibiting glucose reabsorption in the kidney with elimination of glucose by excretion in the urine (glucosuria).
Dapagliflozin (trade name: Forxiga) is an active pharmaceutical ingredient (API) and a selective inhibitor of SGLT2 that is being developed for the treatment of type 2 diabetes mellitus. Marketing approval for dapagliflozin is being sought.
The IUPAC systematic name of dapagliflozin is (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, and is also known as (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-D-glucitolI. Dapagliflozin is a white to off-white powder with a molecular formula of C21H25ClO6 and a molecular weight of 408.87. The structure of dapagliflozin is shown as compound A.

In U.S. Pat. No. 6,774,112 B2, crystalline complexes formed from both the D- or L-enantiomers of natural amino acids and SGLT2 inhibitors are disclosed.
In PCT application WO 2008/002824 A1, crystalline forms of dapagliflozin comprising (S)-propylene glycol (PG), (R)-PG, EtOH, ethylene glycol (EG), 1:2 L-proline, 1:1 L-proline, 1:1 L-proline hemihydrate, and 1:1 L-phenylalanine are disclosed.
Processes for preparing some of the aforesaid crystalline foiins comprising dapagliflozin and various alcohols and diols are also disclosed in the PCT application WO 2008/002824 A1.
Canagliflozin is an API that is an inhibitor of SGLT2 and is being developed for the treatment of type 2 diabetes mellitus.
The IUPAC systematic name of canagliflozin is (2S,3R,4R,5S,6R)-2-{3-[5-[4-fluorophenyl)-thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol, and is also known as (1S)-1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol and 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]henzene. Canagliflozin is a white to off-white powder with a molecular formula of C24H25FO5S and a molecular weight of 444.52. The structure of canagliflozin is shown as compound B.

In US 2008/0146515 A1, a crystalline hemihydrate form of canagliflozin (shown as Compound C) is disclosed, having the powder X-ray diffraction (XRPD) pattern comprising the following 2θ values measured using CuKα radiation: 4.36±0.2, 13.54±0.2, 16.00±0.2, 19.32±0.2, and 20.80±0.2. The XRPD pattern is shown in FIG. 24. A process for the preparation of canagliflozin hemihydrate is also disclosed in U.S. 2008/0146515 A1.

In US 2009/0233874 A1, a crystalline form of canagliflozin is disclosed. FIG. 25 shows the XRPD pattern of the crystalline form in the detailed description, and the characterized XRPD pattern peaks are shown in Table 1 below.
TABLE 1The characterized XRPD pattern peaks of canagliflozin formPosition (2° theta)d-spacing (Å)3.922.88.011.19.79.210.98.113.06.813.96.415.55.715.65.715.95.616.25.517.35.118.34.918.74.718.84.719.14.619.44.620.34.420.94.321.14.221.84.122.53.922.73.923.23.823.43.825.13.625.73.526.33.426.83.327.33.3